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Bisphosphonate and denosumab initiation in older adults in Ontario, Canada: a population-based cohort study

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Abstract

Summary

We provide an update on how commonly prescribed osteoporosis therapies are being initiated in older adults in Ontario. Patients newly prescribed denosumab are older, more often female, and have more comorbidities than those prescribed bisphosphonates. Their characteristics, monitoring, and persistence with prescribed therapy differ from clinical trial participants. Real-world studies on oral bisphosphonates and denosumab might be valuable.

Purpose

To provide a contemporary view on oral bisphosphonate and denosumab prescribing to older adults in routine care.

Methods

Using linked healthcare databases, we conducted a population-based cohort study of adults ≥ 66 years newly prescribed oral bisphosphonates or denosumab between February 2013 and March 2017 in Ontario, Canada. We captured their clinical characteristics, monitoring, and continuous use of prescribed therapies. We illustrate how “real-world” new users of bisphosphonates and denosumab differ from randomized controlled trial (RCT) participants.

Results

There were 107,847 individuals newly prescribed oral bisphosphonates (n = 59,996) or denosumab (n = 47,851) over the study period. Compared with new users of oral bisphosphonates, denosumab users were older (mean age 79.1 vs. 75.7 years), more often female (97.2 vs. 71.8%), from non-rural areas (93.9 vs. 89.9%), and resided in long-term care (10.9 vs. 3.3%). They had more comorbidities including dementia, falls, and fractures.

Following their new prescription, denosumab users had more frequent testing of serum calcium. Duration of continuous use of denosumab was longer than bisphosphonates, and more bisphosphonate users had evidence of treatment discontinuation (56.7 bisphosphonate vs. 33.8% denosumab users discontinued therapy at 365 days). Compared with RCT participants, a higher proportion of “real-world” bisphosphonate and denosumab users had comorbidities including advanced kidney disease.

Conclusion

The clinical characteristics and monitoring of new users of bisphosphonates and denosumab generally align with practice guidelines, product monographs, and drug reimbursement criteria. Given differences between real-world users and RCT participants, there may be a role for safety and effectiveness studies of bisphosphonates and denosumab in routine care.

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Availability of data and material

The analysis was conducted by members of the ICES Western facility (London, Ontario). Alexandra Ouédraogo and Dr. Kristin Clemens are responsible for the data analysis. The protocol can be obtained by emailing Dr. Kristin Clemens at Kristin.Clemens@sjhc.london.on.ca.

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Acknowledgments

The authors thank IMS Brogan Inc. for use of their Drug Information Database.

Funding

This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care  (MOHLTC). It was conducted at ICES Western, which receives core funding from the Academic Medical Organization of Southwestern Ontario (AMOSO), the Schulich School of Medicine and Dentistry (SSMD), Western University, and the Lawson Health Research Institute (LHRI). Dr. K. Clemens received financial support to conduct this study from the Academic Medical Organization of Southwestern Ontario’s Opportunities Fund, and the Department of Medicine at Western University. Parts of this material are based on data and information compiled and provided by the MOHLTC and CIHI. The analyses, conclusions, opinions and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement by ICES, AMOSO, SSMD, LHRI, or the MOHLTC is intended or should be inferred.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Endocrinology and Metabolism, Western University, London, Ontario, Canada

    Kristin K. Clemens & Tayyab Khan

  2. Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada

    Kristin K. Clemens

  3. ICES, Ontario, Canada

    Kristin K. Clemens, Nivethika Jeyakumar & Alexandra M. Ouédraogo

  4. Lawson Health Research Institute, London, Ontario, Canada

    Kristin K. Clemens

  5. Center for Diabetes, Endocrinology and Metabolism, St. Joseph’s Health Care London, 268 Grosvenor Street, London, Ontario, Canada

    Kristin K. Clemens & Tayyab Khan

  6. Department of Medicine, Division of Geriatrics, Western University, London, Ontario, Canada

    Jenny Thain

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  1. Kristin K. Clemens
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  2. Nivethika Jeyakumar
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  3. Alexandra M. Ouédraogo
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  5. Tayyab Khan
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Contributions

KC conceptualized the study, contributed to the design, and interpreted results, and she drafted the manuscript. AO contributed to the design of the study, conducted the analysis, and interpreted results, and she reviewed the manuscript critically. NJ contributed to the design and interpreted results, and she critically reviewed the manuscript. JT contributed to the design of the study and result interpretation, and she reviewed the manuscript critically. TK contributed to the design of the study and result interpretation, and he reviewed the manuscript critically. All authors approved the final version to be published.

Corresponding author

Correspondence to Kristin K. Clemens.

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Conflicts of interest

KC received a research award that was sponsored in part by Astra Zeneca. She has attended Merck sponsored medical conferences. She has received honoraria for delivering Certified Medical Education talks on diabetes from Sutherland Global Services Canada ULC and the Toronto Ontario Knowledge Translation Working Group Inc. TK has attended Merck sponsored conferences. He has received honoraria from Sutherland Global Services Canada ULC, Novo Nordisk Canada, Abbott, Astra Zeneca, Valeant, the Canadian Medical and Surgical Knowledge Translation Research Group, Boehringer Ingelheim, and Amgen. There are no other conflicts of interest to disclose.

Ethics approval

ICES is an independent, non-profit research institute whose legal status under section 45 of Ontario’s Personal Health Information Protection Act (PHIPA) allows it to collect and analyze health care and demographic data, without REB approval or informed consent from participants, for health system evaluation and improvement.

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Clemens, K.K., Jeyakumar, N., Ouédraogo, A.M. et al. Bisphosphonate and denosumab initiation in older adults in Ontario, Canada: a population-based cohort study. Arch Osteoporos 15, 133 (2020). https://doi.org/10.1007/s11657-020-00796-3

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